We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. We have found that in both rat and mouse brains, DJ-1 knockout results in an age-dependent accumulation of hexokinase 1 in the cytosol, away from its usual location at the mitochondria, with subsequent activation of the polyol pathway of glucose metabolism in vivo. Both in the brain and in cultured cells, DJ-1 deficiency is associated with accumulation of the phosphatase PTEN that antagonizes the kinase AKT. In cells, addition of an inhibitor of AKT (MK2206) or addition of a peptide to dissociate association of hexokinases from mitochondria both inhibit the PINK1/parkin pathway, which works to maintain mitochondrial integrity. One consequence of these metabolic changes in knockout animals is likely to be accumulation of advanced glycation endproducts on DNA, RNA and protein. DJ-1 has recently been suggested to be a deglycase for such species and so we have spent some time in the last year evaluating this hypothesis. We do see alterations in glycation products in cancer cells, but are currently evaluating whether we also see the same changes in in vivo models.